Serum tumor markers in chronic kidney disease: as clinical tool in diagnosis, treatment and prognosis of cancers

Figures & data

Figure 1. Schematic presentation of various cancers that are associated with elevated tumor markers. Underlined cancers indicate primary tumors and others imply additional associated malignancies. Note: AFP, alpha-fetoprotein; CEA, carcinoembryonic antigen; HCG, human chorionic gonadotropin; PSA, prostate-specific antigen.

Table 1. Changes of serum tumor markers in NDD-CKD, hemodialysis, peritoneal dialysis, and renal transplant recipients.

Tumor marker	Primary cancer	Predialysis	Hemodialysis (HD)	Peritoneal dialysis	Kidney transplantation	Reliability
PSA	Prostate cancer	↑fPSA,↑%fPSA	↑fPSA,↑%fPSA	↑fPSA,↑% fPSA	↓fPSA,↔tPSA	tPSA in HD fPSA and fPSA/tPSA  ratio with low flux dialyzer mm
CA 15-3	Breast cancer	↑,↔	↑,↔	↑,↔	↑,↔	No reliable for screening
CA 27.29	Breast cancer
CA 19-9	Pancreatic,  biliary tract cancers	↑,↔	↑,↔	↑,↔	↑,↔	Interpret with caution in HD
CA 125	Ovarian cancer	↑,↔	↑,↔	↑	↔	Interpret with caution in HD
CA 72.4	Ovarian cancer
Afamin	Ovarian cancer	No study available			↓ in acute rejection
HE4	Ovarian cancer	↑	↑	↑
AFP	Hepatoma	↔	↔	↔	↔	Reliable in HD
CEA			↑		↑
β2M	LPD, MPD	↑	↑	↑	↓
HCG (β-subunit)	Germ cell tumors	↑	↑	↑	↑	Reliable in HD
Chromogranin A	NET	↑	↑	NA	↑

Note: AFP: alpha-fetoprotein; β2-M: beta-2 microglobulin; CEA: carcinoembryonic antigen; fPSA: free prostate-specific antigen; fPSA: free prostate specific antigen; HCG: human chorionic gonadotropin; HE4: human epididymis protein 4; LPD: lymphoproliferative disorders; mm: membrane; MPD: myeloproliferative disorders; NA: not applicable; NET: neuroendocrine tumors; NDD-CKD; non-dialysis dependent - chronic kidney disease; PSA: prostate-specific antigen; tPSA: total prostate-specific antigen.

Figure 2. Different studies of prostate specific antigen (tumor marker) in chronic kidney disease. Note: AFP: alpha-fetoprotein; CAPD: continuous ambulatory peritoneal dialysis; CKD: chronic kidney disease; %fPSA: percent free prostate-specific antigen; HCG: human chorionic gonadotropin; HD: hemodialysis; PSA: prostate-specific antigen; PSAD: prostate-specific antigen density.

Table 2. Clinical use of tumor markers in screening, diagnosis, follow-up, and monitoring of cancer patients.

Tumor markers	Normal value	Primary tumor	Benign conditions	Remarks
AFP	<5.4 ng/mL	HCC, NSGCT	Cirrhosis, viral hepatitis, pregnancy	No screening, For diagnosis, follow-up (f/u) and monitoring of treatment response
CA 15-3	31 U/mL	Breast cancer	Hepatitis, benign breast or ovarian disease, endometriosis, PID	No screening and diagnosis, but in f/u of metastatic breast cancer treatment is recommended
CA 125	<35 U/mL	Ovarian cancer	Menstruation, pregnancy, fibroids, ovarian cyst, pelvic inflammation, cirrhosis, ascites, endometriosis, pleural and pericardial effusions	No screening except in HOCS For diagnosis of pelvic mass in postmenopausal women and DX of malignant ascites in women with cancer of unknown primary In monitoring is very helpful
CA 19-9	<37 U/mL	Pancreatic and biliary tract cancers	Pancreatitis, biliary disease, cirrhosis	No screening and F/U in diagnosis of selected pancreatic masses Helpful in monitoring
CA 27.29	38 U/mL	Breast cancer	Breast, liver and kidney disorders, ovarian cysts	No screening and diagnosis For F/U of patients at high risk for recurrence (every 4–6 months) For monitoring is helpful
CA 72.4	<3.8 U/mL	Epithelial ovarian carcinoma	Gastric, colon, breast cancers	Less sensitive than CA 125 for EOC
CEA	<2.5 ng/mL in non-smokers <5 ng/mL in smokers	Colorectal cancer	Cigarette smoking, peptic ulcer disease, inflammatory bowel disease, pancreatitis, hypothyroidism, cirrhosis, biliary obstruction	No screening and diagnosis In patients at high risk for recurrence Q2-3 months for at least 2 years, follow-up is recommended Very helpful in monitoring
β-HCG	<5 mIU/mL	NSGCT, GTD	Hypogonadal states, marijuana use	For diagnosis of GTD and cancer of unknown primary origin Follow/up of NSGCT and GTD (monthly for 6–12 months) Monitoring is essential for NSGCT and GTD
PSA	<4 ng/mL	Prostate cancer	Prostatitis, benign prostatic hypertrophy, prostatic trauma, after ejaculation	For screening and DX of adenocarcinoma of unknown primary, DX of prostate mass and positive bone scan For follow-up and monitoring is very helpful
HE4	<150 pmol/L	Ovarian and endometrial cancer	Aging, smokers, older women, renal failure	For screening, diagnosis, F/U and monitoring is helpful
β2-M	1.5–3 mg/L	MM, leukemia Lymphoma	Renal failure, autoimmune diseases, infectious diseases, viral hepatitis	As prognostic factor and predictor of survival
Chromogranin A	<30 ng/mL	NET	Renal failure	For diagnosis of endocrine tumors
Afamin	68 mg/L	Ovarian cancer	Pregnancy, Alzheimer’s disease, multiple sclerosis	As adjunct marker to CA 125 for diagnosis of ovarian cancer
TFF3	<8 ng/mL	Gastric cancers Colorectal cancers		Detection of tumor stages and distant metastasis, predictor of response to chemotherapy in gastrointestinal cancer

Notes: AFP: alpha-fetoprotein; β2-M: beta2-microglobulin; CEA: carcinoembryonic antigen; EOC: epithelial ovarian carcinoma; GTD: gestational trophoblastic disease; HCC: hepatocellular carcinoma; HCG: human chorionic gonadotropin; HOCS: heritable ovarian cancer syndrome; HE4: human epididymis protein 4; MM: multiple myeloma; NET: neuroendocrine tumors; NSGCT: non-seminomatous germ cell tumors; PID: pelvic inflammatory disease; PSA: prostate-specific antigen; TFF3: trefoil family factor.

Table 3. Panel of complementary serum tumor markers in detection of cancer.

Tumor marker	Type of cancer
AFP, CA 125, HCG	Ovarian cancer
CA125, AFP, HE4	Ovarian endometrioma and epithelial ovarian carcinoma
CA 125, HE4	High accuracy for EOC
AFP, chromogranin A	As complementary diagnostic tool in monitoring of  chronic liver disease patients for detection of HCC
CEA, β2-M	Non-small cell lung carcinoma
CA125, Afamin	Adjunct marker for diagnosis of ovarian cancer
CEA, CYFRA 21-1 and SCC	Non-small cell carcinoma
ProGRP, NSE and CEA or CYFRA 21-1	Small cell lung carcinoma
CA 125, CA 27.29, CEA	Breast cancer recurrence
tPSA, fPSA/tPSA, DRE	Prostatic cancer

Note: AFP: alpha-fetoprotein; β2-M: beta-2 microglobulin; CYFRA 21-1: cytokeratin 19 fragments; CEA: carcinoembryonic antigen; DRE: direct rectal examination; EOC: epithelial ovarian carcinoma; fPSA: free prostate-specific antigen; HCC: hepatocellular carcinoma; HCG: human chorionic gonadotropin; HE4: human epididymis protein 4; NSE: neuron-specific enolase; ProGRP: progastrin releasing peptide; PSA: prostate-specific antigen; tPSA: total prostate-specific antigen; SCC: squamous cell carcinoma antigen.